Assessment for response will be made following the National Cancer Institute Working Group (NCIWG) 2008 Chronic Lymphocytic Leukemia (CLL) criteria for response. The primary endpoint for this trial is the combined complete response (CR) and partial response (PR) rate to the protocol therapy at 3 months, which is the end of Cycle 3.

Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Progressive Disease (PD) defined according to NCIWG 2008 CLL Criteria for Response.

Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Confidence intervals for the median and survival rates at different time points will be constructed if needed.

Number of Participants With Overall Survival (OS) [ Time Frame: 36 Months ] [ Designated as safety issue: No ]

Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Relapsed or Refractory CLL/SLL The HiLOG Trial

Brief Summary

The main purpose of this study is to see if the combination of ofatumumab with high dose methylprednisolone followed by additional treatment with ofatumumab and lenalidomide can help people with relapsed or refractory CLL/SLL get rid of their CLL/SLL for a long period of time. Researchers also want to find out if the combination of ofatumumab with methylprednisolone followed by additional treatment with ofatumumab and lenalidomide is safe and tolerable.

Detailed Description

This is a phase II, single institution, and non-randomized study of patients with relapsed or refractory CLL/SLL, utilizing a two-stage trial design. The primary endpoint for this trial is the combined complete and partial response rate at 3 months (after the end of cycle 3) to the protocol therapy. Investigators anticipate this trial will have a complete response and partial response (CR+PR) rate of at least 55%.

A two-stage design is employed for this trial. The null/unacceptable CR+PR response rate is ≤35% while the anticipated true response rate to the protocol treatment is at least 55% for each disease cohort. At the first stage, 25 patients will be accrued to the trial. If 9 or fewer of these patients respond, then the trial will be terminated early and the response rate to the protocol treatment will be deemed unacceptable (≤35%). Otherwise, if more than 9 patients respond during the first stage, an additional 31 patients will be enrolled to this trial during stage 2 for a total of 56 patients. If 25 or fewer of these 56 patients respond to the protocol treatment at the end of stage 2, no further investigation of the protocol treatment is considered warranted. On the other hand, if more than 25 patients out of the 56 enrolled patients respond, the protocol treatment will be considered promising. If the true response rate is ≤35%, the probability of ending the trial at stage 1 is 0.63. If, however, the true response rate is at least 55%, then the probability of ending the trial at stage 1 is only 0.04. This two-stage design has an overall alpha level of 0.047 and a power of 0.90.

For the purpose of interim analysis at the end of stage 1, the objective response will be measured by the end of 3 months (or end of cycle 3) from the start of the protocol treatment prior to the initiation of the combination of ofatumumab with lenalidomide. The accrual will not be suspended while waiting for the results of the interim analysis unless the observed objective response rate among those patients whose objective response data are available is below 30%.

The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)

Other Names:

Revlimid®

IMiD® compound

Study Arm (s)

Experimental: Immunotherapy

Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab.

Interventions:

Drug: High Dose Methylprednisolone (HDMP)

Drug: Ofatumumab

Drug: Lenalidomide

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Active, not recruiting

Enrollment ICMJE

29

Estimated Completion Date

June 2017

Estimated Primary Completion Date

June 2017 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Understand and voluntarily sign an informed consent form

Able to adhere to the study visit schedule and other protocol requirements

Patients must have histologically or cytologically confirmed CD5+/CD20+ B-Cell chronic lymphocytic leukemia or small lymphocytic lymphoma. The diagnosis of CLL is based upon the National Comprehensive Cancer Network (NCCN) guidelines. Any outside pathology slides used as inclusion criteria for the patient will be reviewed at this institution to confirm the diagnosis. The patient must meet all of the following CLL criteria to participate in this study: absolute lymphocyte count > 5000/μL; CD20+ and CD5+; Bone marrow (BM) lymphocytes ≥ 30%; Or previous confirmed diagnosis of CLL/SLL with less than 5000/μl or less than 30% lymphocytes in BM.

Patients are eligible if they have relapsed or refractory CLL/SLL.

All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.

Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin)

Exclusion Criteria:

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form

Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)

Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

Evidence of laboratory Tumor Lysis Syndrome (TLS) by Cairo-Bishop Definition. Patients may be enrolled upon correction of electrolyte abnormalities.

Use of any other experimental drug or therapy within 28 days of baseline

Known hypersensitivity to thalidomide

The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

Any prior use of lenalidomide

Concurrent use of other anti-cancer agents or treatments

Known seropositive for or active viral infection with human immunodeficiency virus (HIV)

Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the patient will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the patient can be included. Patients who are seropositive because of hepatitis B virus vaccine are eligible.

Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibodies (HCAb), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result

Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) are ineligible.

Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient

Gender

Both

Ages

18 Years and older (Adult, Senior)

Accepts Healthy Volunteers

No

Contacts ICMJE

Contact information is only displayed when the study is recruiting subjects